Proteomic strategies to elucidate pathogenic mechanisms of spirochetes
School of Agriculture, Food Science and Veterinary Medicine, University College Dublin, Ireland. . Proteomics. Clinical applications
(Impact Factor: 2.96).
09/2007; 1(9):1185-97. DOI: 10.1002/prca.200700090
Spirochetes are a unique group of bacteria that include several motile and highly invasive pathogens that cause a multitude of acute and chronic disease processes. Nine genomes of spirochetes have been completed, which provide significant insights into pathogenic mechanisms of disease and reflect an often complex lifestyle associated with a wide range of environmental and host factors encountered during disease transmission and infection. Characterization of the outer membrane of spirochetes is of particular interest since it interacts directly with the host and environs during disease and likely contains candidate vaccinogens and diagnostics. In concert with appropriate fractionation techniques, the tools of proteomics have rapidly evolved to characterize the proteome of spirochetes. Of greater significance, studies have confirmed the differential expression of many proteins, including those of the outer membrane, in response to environmental signals encountered during disease transmission and infection. Characterization of the proteome in response to such signals provides novel insights to understand pathogenic mechanisms of spirochetes.
Available from: Sean J Callanan
[Show abstract] [Hide abstract]
ABSTRACT: Leptospirosis is a global zoonotic disease. The causative agent, pathogenic Leptospira species, survives in the renal tubules of chronically infected hosts, from where leptospires are shed via urine into the
environment. Infection of new hosts can present as an array of acute and chronic disease processes reflecting variations in
host-pathogen interactions. The present study was designed to reproduce the carrier phase of infection in Rattus norvegicus, thus facilitating shedding of leptospires in urine. Leptospires shed in urine were collected for proteomic analysis because
these organisms reflect a naturally virulent form of Leptospira associated with infection of new hosts. Experimentally infected rats remained clinically asymptomatic but shed leptospires
in urine for several months at concentrations of up to 107 leptospires/ml of urine. Proteomic analysis of rat urine-isolated leptospires compared to in vitro-cultivated leptospires
confirmed differential protein and antigen expression, as demonstrated by two-dimensional gel electrophoresis and immunoblotting.
Furthermore, while serum from chronically infected rats reacted with many antigens of in vitro-cultivated Leptospira, few antigens of rat urine-isolated Leptospira were reactive. Results confirm that differential protein expression by Leptospira during chronic infection facilitates its persistence in the presence of a specific host antibody response.
Available from: Diane Edmondson
[Show abstract] [Hide abstract]
ABSTRACT: Treponema pallidum subsp. pallidum is the causative agent of syphilis, a sexually transmitted disease characterized by widespread tissue dissemination and chronic infection. In this study, we analyzed the proteome of T. pallidum by the isoelectric focusing (IEF) and nonequilibrating pH gel electrophoresis (NEPHGE) forms of two-dimensional gel electrophoresis (2DGE), coupled with matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) analysis. We determined the identity of 148 T. pallidum protein spots, representing 88 T. pallidum polypeptides; 63 of these polypeptides had not been identified previously at the protein level. To examine which of these proteins are important in the antibody response to syphilis, we performed immunoblot analysis using infected rabbit sera or human sera from patients at different stages of syphilis infection. Twenty-nine previously described antigens (predominantly lipoproteins) were detected, as were a number of previously unidentified antigens. The reactivity patterns obtained with sera from infected rabbits and humans were similar; these patterns included a subset of antigens reactive with all serum samples tested, including CfpA, MglB-2, TmpA, TmpB, flagellins, and the 47-kDa, 17-kDa, and 15-kDa lipoproteins. A unique group of antigens specifically reactive with infected human serum was also identified and included the previously described antigen TpF1 and the hypothetical proteins TP0584, TP0608, and TP0965. This combined proteomic and serologic analysis further delineates the antigens potentially useful as vaccine candidates or diagnostic markers and may provide insight into the host-pathogen interactions that occur during T. pallidum infection.
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.